Decoquinate prodrugs

Abstract

A compound can include a structure having decoquinate coupled to a prodrug moiety, or derivative or isomer or pharmaceutically acceptable salt thereof. The compound can be a decoquinate prodrug. The decoquinate prodrug can have a structure of any of the formulae described herein. The decoquinate prodrug can be synthesized in any manner, such as a synthetic method that includes Scheme 1A or Scheme 1B and Schemes 2, 3, and/or 4. The decoquinate prodrug can be prepared into a pharmaceutical composition with a pharmaceutically acceptable carrier, such as an aqueous composition. The decoquinate prodrug can be used for inhibiting or treating a parasitic infection, such as a malarial infection or a coccidian infection.

1 . A compound comprising:
 a structure having decoquinate coupled to a prodrug moiety, or derivative or isomer or pharmaceutically acceptable salt thereof.   
     
     
         2 . The compound of  claim 1 , wherein the prodrug moiety is coupled to the nitrogen of the decoquinate or derivative or isomer or pharmaceutically acceptable salt thereof. 
     
     
         3 . The compound of  claim 2 , wherein the prodrug moiety is linked to the decoquinate or derivative or isomer or pharmaceutically acceptable salt thereof through a linker. 
     
     
         4 . The compound of  claim 3 , wherein the linker includes a straight aliphatic, branched aliphatic, cyclic aliphatic, heterocyclic aliphatic, substituted aliphatic, unsubstituted aliphatic, saturated aliphatic, unsaturated aliphatic, aromatic, polyaromatic, substituted aromatic, hetero-aromatic, amine, primary amine, secondary amine, tertiary amine, aliphatic amine, carbonyl, carboxyl, amide, ester, amino acid, peptide, polypeptide, sugars, sugar mimic, derivatives thereof, or combinations thereof. 
     
     
         5 . The compound of  claim 2 , wherein structure is one of Formula 1 or Formula 1A or Formula 1B or Formula 1C or Formula 1D or Formula 1E or decoquinate derivative or isomer or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         Prodrug is a prodrug moiety; 
         R 1  and R 2  are independently selected from or include hydrogen, halogens, hydroxyls, alkoxys, straight aliphatics, branched aliphatics, cyclic aliphatics, heterocyclic aliphatics, substituted aliphatics, unsubstituted aliphatics, saturated aliphatics, unsaturated aliphatics, aromatics, polyaromatics, substituted aromatics, hetero-aromatics, amines, primary amines, secondary amines, tertiary amines, aliphatic amines, carbonyls, carboxyls, amides, esters, amino acids, peptides, polypeptides, sugars, sugar mimics, derivatives thereof, wherein the aliphatic groups can include carbon chains, each independently being about 1-20, about 1-10, which carbon chains may be substituted with hetero atoms O, N, S, or P, or R 1  and R 2  form a ring that is aliphatic or aromatic with 3, 4, 5, 6, or 7 carbon and/or hetero atom members in the ring; 
         R 3 , R 4 , and R 5  are independently selected from or include hydrogen, halogens, hydroxyls, alkoxys, straight aliphatics, branched aliphatics, cyclic aliphatics, heterocyclic aliphatics, substituted aliphatics, unsubstituted aliphatics, saturated aliphatics, unsaturated aliphatics, aromatics, polyaromatics, substituted aromatics, hetero-aromatics, amines, primary amines, secondary amines, tertiary amines, aliphatic amines, carbonyls, carboxyls, amides, esters, amino acids, peptides, polypeptides, sugars, sugar mimics, derivatives thereof, wherein the aliphatic groups can include carbon chains, each independently being about 1-20, about 1-10, which carbon chains may be substituted with hetero atoms O, N, S, or P; 
         the linker includes a straight aliphatic, branched aliphatic, cyclic aliphatic, heterocyclic aliphatic, substituted aliphatic, unsubstituted aliphatic, saturated aliphatic, unsaturated aliphatic, aromatic, polyaromatic, substituted aromatic, hetero-aromatic, amine, primary amine, secondary amine, tertiary amine, aliphatic amine, carbonyl, carboxyl, amide, ester, amino acid, peptide, polypeptide, sugars, sugar mimic, derivatives thereof, or combinations thereof; and 
         n is an integer. 
       
     
     
         6 . The compound of  claim 5 , wherein structure is one of Formula 2 or Formula 2A or Formula 2B or Formula 2C or Formula 2D or Formula 2E or decoquinate derivative or isomer or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         PO is one of PO 1  or PO 2 ; and 
         X is a cation 
       
       
         
           
           
               
               
           
         
       
     
     
         7 . The compound of  claim 5 , wherein structure is one of Formula 3 or Formula 3A or Formula 3B or Formula 3C or Formula 3D or Formula 3E or decoquinate derivative or isomer or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein EPO 1  is: 
       
       
         
           
           
               
               
           
         
       
     
     
         8 . The compound of  claim 5 , wherein structure is one of Formula 4 or Formula 4A or Formula 4B or Formula 4C or Formula 4D or Formula 4E or decoquinate derivative or isomer or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         X is a cation; and 
         EPO 2  is: 
       
       
         
           
           
               
               
           
         
       
     
     
         9 . The compound of  claim 5 , wherein structure is Formula 5 or decoquinate derivative or isomer or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound of  claim 5 , wherein structure is Formula 6 or decoquinate derivative or isomer or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         11 . A pharmaceutical composition comprising:
 a prodrug structure having decoquinate coupled to a prodrug moiety, or derivative or isomer or pharmaceutically acceptable salt thereof; and   a pharmaceutically acceptable carrier.   
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein the pharmaceutically acceptable carrier includes an aqueous composition. 
     
     
         13 . The pharmaceutical composition of  claim 11 , further comprising another anti-malarial agent. 
     
     
         14 . The pharmaceutical composition of  claim 11 ,
 wherein prodrug structure is one of Formula 1 or Formula 1A or Formula 1B or Formula 1C or Formula 1D or Formula 1E or decoquinate derivative or isomer or pharmaceutically acceptable salt thereof:   
       
         
           
           
               
               
           
         
         wherein: 
         Prodrug is a prodrug moiety; 
         R1 and R2 are independently selected from or include hydrogen, halogens, hydroxyls, alkoxys, straight aliphatics, branched aliphatics, cyclic aliphatics, heterocyclic aliphatics, substituted aliphatics, unsubstituted aliphatics, saturated aliphatics, unsaturated aliphatics, aromatics, polyaromatics, substituted aromatics, hetero-aromatics, amines, primary amines, secondary amines, tertiary amines, aliphatic amines, carbonyls, carboxyls, amides, esters, amino acids, peptides, polypeptides, sugars, sugar mimics, derivatives thereof, wherein the aliphatic groups can include carbon chains, each independently being about 1-20, about 1-10, which carbon chains may be substituted with hetero atoms O, N, S, or P, or R1 and R2 form a ring that is aliphatic or aromatic with 3, 4, 5, 6, or 7 carbon and/or hetero atom members in the ring; 
         R3, R4, and R5 are independently selected from or include hydrogen, halogens, hydroxyls, alkoxys, straight aliphatics, branched aliphatics, cyclic aliphatics, heterocyclic aliphatics, substituted aliphatics, unsubstituted aliphatics, saturated aliphatics, unsaturated aliphatics, aromatics, polyaromatics, substituted aromatics, hetero-aromatics, amines, primary amines, secondary amines, tertiary amines, aliphatic amines, carbonyls, carboxyls, amides, esters, amino acids, peptides, polypeptides, sugars, sugar mimics, derivatives thereof, wherein the aliphatic groups can include carbon chains, each independently being about 1-20, about 1-10, which carbon chains may be substituted with hetero atoms O, N, S, or P; 
         the linker includes a straight aliphatic, branched aliphatic, cyclic aliphatic, heterocyclic aliphatic, substituted aliphatic, unsubstituted aliphatic, saturated aliphatic, unsaturated aliphatic, aromatic, polyaromatic, substituted aromatic, hetero-aromatic, amine, primary amine, secondary amine, tertiary amine, aliphatic amine, carbonyl, carboxyl, amide, ester, amino acid, peptide, polypeptide, sugars, sugar mimic, derivatives thereof, or combinations thereof; and 
         n is an integer. 
       
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein structure is one of Formula 2 or Formula 2A or Formula 2B or Formula 2C or Formula 2D or Formula 2E or decoquinate derivative or isomer or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         PO is one of PO 1  or PO 2 ; and 
         X is a cation 
       
       
         
           
           
               
               
           
         
       
     
     
         16 . The pharmaceutical composition of  claim 14 , wherein structure is one of Formula 3 or Formula 3A or Formula 3B or Formula 3C or Formula 3D or Formula 3E or decoquinate derivative or isomer or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein EPO 1  is: 
       
       
         
           
           
               
               
           
         
       
     
     
         17 . The pharmaceutical composition of  claim 14 , wherein structure is one of Formula 4 or Formula 4A or Formula 4B or Formula 4C or Formula 4D or Formula 4E or decoquinate derivative or isomer or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         X is a cation; and 
         EPO 2  is: 
       
       
         
           
           
               
               
           
         
       
     
     
         18 . The pharmaceutical composition of  claim 14 , wherein structure is Formula 5 or decoquinate derivative or isomer or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         19 . The pharmaceutical composition of  claim 14 , wherein structure is Formula 6 or decoquinate derivative or isomer or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         20 . A method of inhibiting or treating a parasitic infection, the method comprising:
 providing a subject in need of inhibition or treatment for a parasitic infection; and   administering to the subject a pharmaceutical composition containing a therapeutically effective amount of a decoquinate prodrug.   
     
     
         21 . The method of  claim 20 , wherein the parasitic infection is malaria. 
     
     
         22 . The method of  claim 20 , wherein the parasitic infection is a coccidian infection.